Role of elastin in regulating vascular smooth muscle cell differentiation during development and disease

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Title Role of elastin in regulating vascular smooth muscle cell differentiation during development and disease
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Karnik, Satyajit Kanchan
Date 2004-05
Description Vascular proliferative diseases such as atherosclerosis and coronary restenosis are leading causes of morbidity and mortality in developed nations. Common features associated with these heterogeneous disorders involve abnormal proliferation and migration of vascular smooth muscle cells into the arterial lumen, leading to neointimal formation and vascular stenosis. Unlike other cell types, vascular smooth muscle cells (VSMCs) possess the unique ability to modulate their phenotype based upon extracellular cues. During this modulation, VSMCs undergo a transformation from an immature, proliferative state, to a mature, quiescent one. This modulation occurs during arterial development and forms the basis of obstructive vascular disease. The ability to regulate this process has potential therapeutic implications. Yet, the external stimuli, that govern this process are unknown. Our hypothesis was that the extracellular matrix protein, elastin, regulated VSMC phenotype. This hypothesis was based on studies of Eln -/- mice. Mice lacking the elastin protein die at postnatal day 3.5 from an overproliferation and invasion of the VSMCs lining the neointimal layer of elastic arteries. This lead us to propose that elastin controlled the modulation of VSMCs from an immature to a mature state during arterial development. The disruption of this interaction could thus lead to arterial disease. Here, we demonstrate that elastin functions in an autocrine manner, providing a critical cue for VSMCs during development. We argue that elastin communicates with the VSMC interior, through nonintegrin, nonreceptor tyrosine kinase, pertussis toxin-sensitive G protein coupled receptors. The distal portion of this pathway involves lowered cAMP levels, GiRK activation, and RhoA activation. This works leads us to proposing rudimentary elastin signal transduction pathway and gives us a system to identify an elastin receptor.
Type Text
Publisher University of Utah
Subject Physiology; Proteins; Receptors
Subject MESH Elastin; Cell Differentiation
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "The role of elastin in regulating vascular smooth muscle cell differentiation during development and disease." Spencer S. Eccles Health Sciences Library. Print version of "The role of elastin in regulating vascular smooth muscle cell differentiation during development and disease." available at J. Willard Marriott Library Special Collection. QP6.5 2004 .K37.
Rights Management © Satyajit Kanchan Karnik.
Format application/pdf
Format Medium application/pdf
Format Extent 4,248,242 bytes
Identifier undthes,4877
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 4,248,272 bytes
ARK ark:/87278/s6q24202
Setname ir_etd
ID 190942
Reference URL https://collections.lib.utah.edu/ark:/87278/s6q24202
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